This section introduces aspects that may help facilitate a better understanding of the disclosure. Accordingly, these statements are to be read in this light and are not to be understood as admissions about what is or is not prior art.
Infants who are born before the full 40-week gestation period are considered “preterm” (if born before week 37 of pregnancy) or “premature” (if born before 34-week gestation). One of the major health risks associated with preterm/premature births is underdeveloped lungs, which cause high infant mortality. Infants born before the 37th week of gestation are born without alveolar structures, and have low production of lung surfactants. As a result, preterm/premature infants struggle to breathe, and, without proper treatments, die within a few days. This respiratory failure is named as Respiratory Distress Syndrome (RDS), or also known as Hyaline Membrane Disease, misnamed in the past due to the misconception of the cause of this disease as being of viral origin.
In old days when RDS was misnamed as Hyaline Membrane Disease, it was the leading cause of infant death in the United States with a higher death rate than Pneumonia and Influenza. However, now-a-days with skilled physicians and three well-established treatment methods, the mortality rate from RDS decreased substantially. The three treatments are performed in stages where if the earlier treatment is successful the next treatment is not performed. The first treatment for RDS is a prevention treatment where steroid is given to the mother 24 hours prior to labor to increase the production of the infant's own lung surfactants. Clinical data on steroid treatment with betamethasone has shown effective reduction of RDS occurrence from 25.8% to 9.0%. The second treatment, Surfactant Replacement Therapy (SRT), involves intratracheal injection of animal extracted lung surfactants into the infant's lungs immediately after birth. The development of successful SRT has been the main driver in lowering the RDS-related mortality rate, and, due to its high effectiveness, is included in the Essential Drug List of the World Health Organization. The third treatment involves mechanical ventilation in which infants are put under nasal continuous/discontinuous positive airway pressure treatment to increase the oxygen levels in the lungs. Treatment using mechanical ventilation is the oldest treatment method for treating RDS. Its initial clinical testing was shown to reduce the mortality rate from 80% to 20%. However, oxygen poisoning and mechanical damage to the lungs remain an adverse effect. Out of the three treatment methods, SRT is the most reliable treatment directly resolving the underlying cause of RDS with no adverse effect reported so far. Improvement of RDS treatment is expected to be accompanied with advancements in SRT practice.
Despite the success in the domestic reduction of the RDS-related mortality for preterm and premature infants, world-wide, especially in developing countries, RDS is currently still one of the leading causes of neonatal death due to the high treatment cost and complex treatment procedures. Although highly effective, the cost of SRT is extremely high; the cost of SRT therapeutics alone exceeds the per capita GNP in some countries. The economical imbalance affecting the use of SRT is clearly shown in FIG. 1 where countries in Central Asia and Africa do not have full access to SRT. Development of lower-cost RDS therapeutics with simpler treatment procedures that do not require highly skilled physicians and advanced neonatal intensive care units (NICU) will solve this problem, and will reduce the leading cause of neonatal death world-wide. It should be noted that even in the United States, in some rural areas, preterm and premature infants are exposed to risks of RDS-related mortality due to the lack of skilled physicians and needed medical resources such as NICU facilities. In regions where SRT is not practicable, treatment mainly relies on mechanical ventilation. There is therefore an unmet need for a better SRT technology.
Lung Surfactant (LS) complication can also occur in adults and pediatrics. The most severe form of respiratory failure is termed acute respiratory distress syndrome (ARDS). ARDS is a physiological syndrome that involves multiple risk factors such as sepsis, pneumonia, aspiration-induced lung injury, lung contusion, and massive transfusion. The annual US prevalence of ARDS is 190,000, and despite modern critical care, the mortality rate is ˜40%. Regardless of the origin, ARDS patients exhibit increased protein-rich exudates and inflammation in the alveoli, which result in inactivation and reduced production of lung surfactant. With the success in treatment of neonatal RDS (NRDS) infants with therapeutic LSs, a number of clinical trials investigated their efficacy in treating ARDS patients. Unfortunately, the results from large-scale clinical trials have indicated that current therapeutic LSs are not effective in treating adult ARDS. However, there were two critical issues with previous clinical trials. (1) Current therapeutic LSs are not designed to be resistant to deactivation caused by serum proteins. (2) The LS dose levels used were inappropriate. Both of these factors are related to the mechanism of LS's surface activity.
There is a need for an alternative method for ARDS treatment: the use of therapeutic surfactants that are resistant to deactivation by proteins. All currently available lipid/protein-based LSs fall short in this regard.